The present invention relates to a dental composition that exhibits long-term stability, on the order of greater than 12 months, and can be conveniently formulated as in a paste-paste or paste-liquid system. In one embodiment, the composition contains, among other components, at least one polyacid and at least one redox catalyst. At least one of the polyacid and redox catalyst exist in a disperse phase.
In general, a dental composition such as glass ionomer cements comprise ionic polymers and reactive glasses. The mixing of the two components in an aqueous environment initiates a setting reaction. Glass ionomer cements find utility in dental and medical applications, where the cements are used on, e.g., tooth and bone structures. Conventional glass ionomer cements have been supplied as a two-part powder-liquid system, where an ionic polymer (typically polyacrylic acid) is dissolved in water and a reactive glass (typically an acid-reactive glass) is in powder form. See, e.g. Robert G. Craig, Restorative Dental Materials, 9th edition (1993) at page 197.
One advancement over the conventional glass ionomer cements is the hybrid ionomer cement, also known as resin modified ionomer cement. It contains, among other components, at least one polymerizable compound and polymerization initiators. The hybrid ionomer cement typically has liquid and powder components. The liquid component can contain an ionic polymer such as polyacrylic acid (the acid may be functionalized with ethylenically unsaturated moieties), a polymerizable compound, water, and optional redox catalysts, which functions as part of the initiating system. The powder component can contain basic-reactive glass and redox catalysts, such as oxidizing and reducing agents.
It has been recognized by those skilled in the art that a powder-liquid system, such as those of conventional or hybrid glass ionomer cement, can present drawbacks. For example, extra skill and time may be required to dispense proportionate amounts of the powder and the liquid and mixing them to form the cement.
To overcome the disadvantages of the powder-liquid system, some skilled in the art have investigated alternative systems. For example, U.S. Pat. No. 6,136,885 (Rusin et al.) discloses a ionomer cement system comprising (a) an organic composition having a liquid ingredient that is free of water, and (b) an aqueous composition having a liquid ingredient comprising water.
In U.S. Pat. No. 5,154,762 (Mitra et al.), a dental cement contains water, acid-reactive filler, water-miscible acidic polymer, ethylenically-unsaturated moiety, photoinitiator, water-soluble reducing agent, and water-soluble oxidizing agent. Two part paste-paste cements were disclosed at column 2, lines 58 to 66.
While the foregoing dental compositions may have been us compositions are sought.
In brief summary, in one embodiment, the present invention provides a dental composition comprising (a) a part A comprising at least one polyacid and at least one polymerizable component and (b) a part B comprising water. The composition further comprises an oxidizing agent, a reducing agent (both being part of a redox catalyst system), and reactive fillers in at least one of part A or part B. One uniqueness of the present invention is that at least one of the following components exist in a disperse phase: the polyacid, the oxidizing agent, and the reducing agent.
In use, when parts A and B are mixed together to form the inventive composition, the reactive filler, the polyacid, and the oxidizing agent become chemically reactive. Upon mixing, parts A and B are at least partially miscible with one another. Parts A and B can be supplied in paste-paste form or paste-liquid form.
The inventive composition has shelf stability on the order of months, typically at least 12 months. The inventors have discovered that such long-term stability can be achieved when at least one of the following components is in the disperse phase: the polyacid and the redox catalyst.
The term xe2x80x9cdisperse phasexe2x80x9d means generally a two-phase system where one phase contains discrete particles distributed throughout a bulk substance, the particles being the disperse phase, and the bulk substance being the continuous phase. In one inventive embodiment, the continuous phase is the polymerizable component and at least a portion of the polyacid and/or redox catalyst exists as the discrete particles. By xe2x80x9cdisperse phase,xe2x80x9d it is also meant that not necessarily the entire polyacid and/or redox catalyst need to be insoluble in the polymerizable component. Some of the polyacid and/or redox catalyst can be soluble therein. The dispersed particles are generally less than about 60 micrometers in average diameter.
One skilled in the art can determine whether the polyacid and/or the redox catalysts exist in a disperse phase by using any number of separation techniques, such as centrifugation or filtration. In these techniques, if there is a disperse phase, it will phase separate out of the bulk substance, either catching on the filter paper in the case of filtration or phase separate and settle out in the case of centrifugation. The separation test method should be performed when the polyacid and/or redox catalyst is the presence of a polymerizable component. That is, the other components of the inventive dental composition, such as the filler, should not be part of the system during testing to determine the presence of a disperse phase.
Although numerous references have disclosed the use of polyacid and redox catalyst in ionomer cement compositions, the inventors are not aware of any reference that disclose or suggest using either one in a disperse phase. The inventors have been able to formulate resin modified ionomer cement compositions having stability exceeding 12 months.
The inventors have further discovered an alternative approach to achieving long-term stability in the dental composition. This approach uses a particular monoacid that is dissolved in the polymerizable component. The monoacid, as the name implies, contains acid functionality, but does not contain hydroxyl functionality, particularly primary or secondary hydroxyl groups. When using this approach it is not necessary to have the polyacid or the redox catalyst in a disperse phase.
Instabilities may exist in conventional and resin modified ionomer cement systems. For example, in some systems, peroxide oxidizing agents can react with compounds having acid functionality when both are solubilized, i.e., dissolved in some carrier, such as water, hydroxylic solvents, or short chain hydroxylic monomers all of which are widely used in glass ionomer cements. Oxidizing agents and reducing agents can react in the presence of water and initiate the setting of the polymerizable component unless the agents are first encapsulated. The polyacid can react with reactive fillers, especially with fluoroaluminosilicate (FAS) glass in the presence of water. The polyacid can react many reducing agents, such as amines and/or sulfinates, to induce premature free radical polymerization. Thus, the inventors have devised a unique solution to the instabilities that may be present in a dental composition by deliberately putting the polyacid and/or the redox catalyst in a disperse phase or by using a particular type of monoacid dissolved in the polymerizable component.
The inventive dental composition can be used in various applications, such as dental adhesives, artificial crowns, anterior or posterior fillings, casting materials, cavity liners, cements, coating compositions, mill blanks, adhesives and cements for affixing orthodontic brackets and appliances, endodontic cements, restoratives, prostheses, and sealants. The composition is especially suited for use as a cement. The composition can be placed in the mouth and cured in situ. Alternatively, it can be fabricated in a prosthesis outside the mouth and subsequently adhered in place in the mouth.
The inventive dental composition can be formulated as a one- or a two-components system. The two-component system is preferred. One suitable two-component system comprises (a) a part A comprising at least one polyacid compound, at least one polymerizable component, and at least one oxidizing agent; and (b) a part B comprising water, reactive fillers, and at least one reducing agent. In such a two-component system, at least one of the polyacid compound, oxidizing agent, and reducing agent is dispersed in the polymerizable component. The composition comprises about 5 to 35 parts water, based on the total weight of the composition. Each component is discussed below in detail.
Polyacid
The polyacid preferably resides in part A. Useful polyacids are polymers having sufficient pendent ionic groups to undergo a setting reaction in the presence of reactive fillers and water. The polyacid may or may not contain polymerizable groups to enable the resulting composition to be cured when exposed to redox and/or photoactivated polymerization initiators. The polyacid should be partially or fully insoluble in the polymerizable component. The polyacid constitutes at most about 50 parts, preferably about 5 to 25 parts of the total composition.
Examples of suitable polyacid compounds include polymers derived from the following acid: acrylic acid, methacrylic acid, itaconic acid, maleic acid, glutaconic acid, aconitic acid, citraconic acid, mesaconic acid, fumaric acid, tiglic acid, and combinations thereof. Preferred polyacids are described in U.S. Pat. No. 5,130,347 (Mitra). A particularly preferred polyacid is described in Example 11 of U.S. Pat. No. 5,130,347 and when used, this polyacid constitutes at most about 30, preferably about 5 to 25 parts by weight of the total composition.
Polymerizable Component
The polymerizable component resides in part A and/or part B. The inventive cement contains about 5 to 75, preferably about 10 to 50, more preferably about 15 to 45 parts by weight of the polymerizable component, based on the total weight of the composition. Useful polymerizable components are monomers, oligomers, or polymers containing a polymerizable group selected from the following: free radically polymerizable groups, cationically polymerizable groups, or mixtures thereof. It is within the scope of this invention that a polyacid functions as a polymerizable component. The polymerizable component is incapable of fully dissolving the polyacid or the redox catalyst, although partial solubility is possible. The polymerizable component is partially or fully water soluble, meaning that the component is soluble in water at concentrations of at least 3% by weight.
The polymerizable component has a molecular weight between about 100 to 5000, and preferably, between about 200 and 1000. Mixtures of both higher and lower molecular weight materials are also contemplated as providing special benefits in handling properties and ultimate cure material physical properties. In some embodiments, at least some of the polymerizable component is lower in viscosity relative to the other ingredients of the composition thus functioning to lower the viscosity of the overall uncured composition. One skilled in the art can vary the viscosity of the uncured composition depending on its intended application.
The suitablility of a polymerizable component can depend on which side it resides. When it resides in part A, useful polymerizable components include: (i) partially water soluble monomers, (ii) non-hydroxylic functional monomers that are partially water soluble (such as polyethylene glycol dimethacrylate and tetrahydrofurfuryl methacrylate), or (iii) longer chain hydroxylic functional monomers that do not fully solubilize the polyacid and/or the redox catalyst. Of these, the non-hydroxylic functional monomers are preferred. The polymerizable components of Part A are preferably partially or fully water soluble.
When residing in part B, the polymerizable component can be any monomer that, when combined with water, generate a single liquid phase. This criteria does not imply that any individual monomer has to be water soluble, but that a combination of monomers be water soluble. Examples of suitable polymerizable component include 2-hydroxyethyl methacrylate (HEMA), glycerol dimethacrylate (GDMA), and glycerol monomethacrylate (GMMA).
Other suitable polymerizable components include monomers that contain acid functionality. Illustrative examples include the bis-isocyanatoethylmethacrylate derivative of bis-hydroxymethylpropionic acid (PDMA) or the bis-isocyanatoethylmethacrylate derivative of citric acid (CDMA). Unlike the polyacids described above, which preferably exist as partially or fully dispersed components, these acid-functionalized polymerizable components may be fully dissolved in the polymerizable components such as polyethylene glycol dimethacrylate and tetrahydrofurfural methacrylate. These acid-functionalized polymerizable components, however, do not contain hydroxyl functionality, particularly primary or secondary hydroxyl functionality. They contain multiple polymerizable groups and can participate in several types of curing chemistry such as the glass ionomer chemistry and the free radical initiated polymerization chemistry. They can be used to enhance various physical and handling properties of the inventive composition. When used they constitute from about 1 to 35 parts of the total composition.
Fillers
Two general classes of fillers are used in the present invention: reactive fillers and non-reactive fillers. The fillers can reside in either part A and/or part B. Regardless of the type of filler used, it should be non-toxic and suitable for use in the mouth. The filler can be radiopaque or non-radiopaque.
Suitable reactive fillers for use in the present inventive cement include those that are commonly used with glass ionomer cements. Illustrative examples of suitable reactive fillers include metal oxides such as zinc oxide and magnesium oxide, and non-leachable glasses, such as those described in U.S. Pat. Nos. 3,655,605; 3,814,717; 4,143,018; 4,209,434; 4,360,605; and 4,376,835.
Preferably the reactive filler is finely divided so that it can be mixed conveniently with other ingredients and used in the mouth. The average particle diameter for the filler is about 0.2 to 15 micrometers, preferably about 0.2 to 10 micrometers, as measured using, e.g., a sedimentation analyzer.
Preferred reactive fillers are acid-reactive. Suitable acid-reactive fillers include metal oxides, metal salts, and glasses. Preferred metal oxides include the oxides of barium, calcium, magnesium, and zinc. Preferred metal salts include salts of multivalent cations, e.g., aluminum acetate, aluminum chloride, calcium chloride, magnesium chloride, zinc chloride, aluminum nitrate, barium nitrate, calcium nitrate, magnesium nitrate, strontium nitrate, and calcium fluoroborate. Preferred glasses include borate glasses, phosphate glasses, and fluoroaluminosilicate glasses (FAS), the last being particularly preferred. Various forms of calcium phosphates such as hydroxyapatite (Ca10 (PO4)6 (OH)2) or monetite (CaHPO4) can also be used. Another preferred reactive filler is the class of bioactive glasses and glass-ceramics, which are believed to attach directly by chemical bonding to bone and other biological tissues. Examples of such materials are disclosed in U.S. Pat. No. 5,074,916. Mixtures of these reactive fillers can be used.
If desired, the reactive filler can be subjected to surface treatment as described in U.S. Pat. No. 6,136,885, e.g., at column 8, lines 35 to 42. The surface of the reactive filler can be treated with a coupling agent. Suitable coupling agents include gamma-methacryloxypropyltrimethoxysilane, gamma-mercaptopropyltriethoxysilane, gamma-aminopropyltrimethoxysilane, and the like.
The amount of reactive filler used should be sufficient to provide a composition having desirable mixing and handling properties before cure and good performance after cure. The reactive filler represents less than about 90%, preferably about 15% to 75%, more preferably about 30% to 60% by weight of the total weight of the composition.
As stated above, non-reactive fillers can be used in the present invention. Non-reactive fillers can be selected from one or more of any material suitable for use in medical applications. The filler is finely divided and preferably has a maximum particle diameter less than about 50 micrometers and an average particle diameter less than about 10 micrometers. The filler can have a unimodal or polymodal (e.g., bimodal) particle size distribution. The filler can be an inorganic material. It can also be a crosslinked organic material that is insoluble in the polymerizable component.
Illustrative examples of suitable non-reactive inorganic fillers are naturally occurring or synthetic materials such as quartz, nitrides (e.g., silicon nitride), glasses derived from, e.g., Ce, Sb, Sn, Zr, Sr, Ba, and Al. Other glasses include colloidal silica, feldspar, borosilicate glass, kaolin, talc, titania, and zinc glasses. Also useful are low Mohs hardness fillers such as those described in U.S. Pat. No. 4,695,251 and submicron silica (e.g., pyrogenic silicas such as the AEROSIL series OX 50, 130, 150, and 200 silicas commercially available from Degussa Co., Germany and CAB-O-SIL M5 silica sold by Cabot Corp., Tuscola, Ill.). Illustrative examples of suitable non-reactive organic filler particles include filled or unfilled pulverized polycarbonate, polyepoxides, and the like. Alloys of silver, copper or tin can also be used as non-reactive fillers. Mixtures of the non-reactive fillers can also be used.
Redox Catalysts
A preferred mode of initiating the polymerization reaction uses oxidizing and reducing agents as a redox catalyst system. The catalyst enables the ionomer cement composition to cure via a redox reaction. The oxidizing and reducing agents can reside in either parts A or B. These agents can exist in a disperse phase. Preferably, the oxidizing agent exists as a disperse phase in part A and the reducing agent is soluble in part B, although the reducing agent can exist as a disperse phase in part B. Various redox catalyst systems and their use in ionomer cements are described in U.S. Pat. No. 5,154,762, e.g., at column 5, line 32 to column 6, line 13. If desired, the reducing and/or oxidizing agents can be microencapsulated, as described in U.S. Pat. No. 5,154,762, e.g., at column 6, line 13 to column 7, line 11.
The oxidizing agent should react with or otherwise cooperate with the reducing agent to produce free radicals. The free radicals are capable of initiating polymerization of the ethylenically unsaturated moiety, which may possibly be present from the polyacid and/or from the polymerizable component. The oxidizing and reducing agents preferably are present in an amount sufficient to permit an adequate free radical reaction rate. For example, in one embodiment, the inventive composition can comprise from about 0.1 to 5.0 parts oxidizing agent, and from about 0.05 to 5.0, preferably about 0.05 to 3.0 parts reducing agent, based on the total weight of the composition.
Suitable oxidizing agents include persulfates such as sodium, potassium, ammonium, and alkyl ammonium persulfates. Other suitable oxidizing agents include peroxides, such as benzoyl peroxide and lauroyl peroxide, and hydroperoxides such as cumene hydroperoxide, tert-butyl hydroperoxide, tert-amyl hydroperoxide, and 2,5-dihydroperoxy-2,5-dimethylhexane. Yet other suitable oxidizing agents include salts of cobalt (III), iron (III), terium (IV), copper (II), perboric acid and its salts, and salts of a permanganate anion. Combinations of the oxidizing agents can be used.
Suitable reducing agents include amines (preferably aromatic amines), ascorbic acid, metal complexed ascorbic acid, cobalt (II) chloride, ferrous chloride, ferrous sulfate, hydrazine, hydroxylamine, oxalic acid, thiourea and derivatives thereof, barbituric acid and derivatives thereof, and salts of dithionite, thiosulfate, sulfite anion, and aromatic sulfinates, such as benzene sulfinate and toluene sulfinate.
Photoinitiators
The inventive cement system may contain one or more suitable photoinitiators that act as a source of free radicals when activated. The photoinitiators can reside in part A and/or part B. Such initiators can be used alone or in combination with one or more accelerators and/or sensitizers.
The photoinitiator should be capable of promoting free radical crosslinking of the ethylenically unsaturated moiety on the polymerizable component and/or the polyacid on exposure to light of a suitable wavelength and intensity. The photoinitiator should be shelf stable and free of undesirable coloration, thereby allowing it to be stored and used under typical dental conditions. Visible light (about 400 to 800 nm wavelength) photoinitiators are preferred. The photoinitiator is preferably partially or fully water soluble or water miscible. Photoinitiators having polar groups usually have a sufficient degree of water solubility or water miscibility. The photoinitiator frequently can be used alone. Typically, however, it is used in combination with a suitable donor compound or a suitable accelerator (e.g., amines, peroxides, phosphorous compounds, ketone and alpha-diketone compounds).
Suitable visible light-induced initiators include camphorquinone, which is typically combined with a suitable hydrogen donor. Other suitable visible light-induced initiators include diaryliodonium simple or metal complex salts, chromophore-substituted halomethyl-s-triazines and halomethyl oxadiazoles. Preferred candidates include combinations of an alpha-diketone, e.g., camphorquinone, and a diaryliodonium salt, e.g., diphenyliodonium chloride, bromide, iodide or hexafluorophosphate, with or without additional hydrogen donors (such as sodium benzene sulfinate, amines, and amine alcohols). Other suitable visible light initiator systems may include alternative sensitizers compounds such as fluorone dyes, ketocoumarins, and the like.
Free-radical initiators useful in the invention, e.g., those that are photochemically active in the wavelength region of greater than 400 to 800 nm, also may include the class of acylphosphine oxides, as described in European Patent Application No. 173567. Such acylphosphine oxides are of the general formula
(R1)2P(xe2x95x90O)C(xe2x95x90O)xe2x80x94R2
wherein each R1 individually can be a hydrocarbyl group such as alkyl, cycloalkyl, aryl, and aralkyl, any of which can be substituted with a halo-, alkyl- or alkoxy-group, or the two R1 groups can be joined to form a ring along with the phosphorous atom, and wherein R2 is a hydrocarbyl group, an S-, O-, or N-containing five- or six-membered heterocyclic group, or a xe2x80x94Zxe2x80x94C(xe2x95x90O)xe2x80x94P(xe2x95x90O)xe2x80x94(R1)2 group, wherein Z represents a divalent hydrocarbyl group such as alkylene or phenylene having from 2 to 6 carbon atoms.
Preferred acylphosphine oxides useful in the invention are those in which the R1 and R2 groups are phenyl or lower alkyl- or lower alkoxy-substituted phenyl. By xe2x80x9clower alkylxe2x80x9d and xe2x80x9clower alkoxyxe2x80x9d is meant such groups having from 1 to 4 carbon atoms. Most preferably, the acylphosphine oxide is bis(2,4,6-trimethylbenzoyl)phenyl phosphine oxide (IRGACURE 819, Ciba Specialty Chemicals, Tarrytown, N.Y.).
Preferred ultraviolet light induced photoinitiators include ketones such as benzyl and benzoin, and acyloins and acyloin ethers. Preferred commercially available candidates include IRGACURE 651, which is 2-dimethyoxy-2-phenylacetophenone, and benzoin methyl ether (or 2-methoxy-2-phenylacetophenone), both from Ciba-Geigy Corp., Basel, Switzerland.
The photoinitiator should be present in an amount sufficient to provide the desired rate of photopolymerization. This amount will depend in part on the light source, the cement layer thickness that will be exposed to the light source, and the extinction coefficient of the photoinitiator. Typically, the photoinitiator is present at about 0.005% to 5%, preferably about 0.05% to 1% by weight, based on the total weight of the composition.
For photocurable ionomers that are polymerized by a cationic mechanism, suitable initiators include salts that are capable of generating cations such as the diaryliodonium, triarylsufonium, and aryldiazonium salts.
Advantageously, having three cure mechanisms in the inventive cement (photocure, dark cure through a redox reaction, and ionic cure) facilitates thorough, uniform cure. Cements using three modes of cure have particular utility in clinical applications where cure of a conventional light-curable composition may be difficult to achieve. Such applications include, e.g., deep restorations, large crown build-ups, endodontic restorations, luting of metallic crowns or other light-impermeable prosthetic devices to teeth, and other restorative applications in inaccessible areas of the mouth.
Miscellaneous Components
The inventive composition may optionally comprise additional adjuvants suitable for use in the oral environment, including colorants, inhibitors, accelerators, flavorants, anti-microbials, fragrance, stabilizers (including free radical stabilizers), viscosity modifiers, submicron silica particles, and modifiers or additives that impart fluorescence and/or opalescence.
Modifying agents prolonged working time. The term xe2x80x9cworking timexe2x80x9d refers to the time between the beginning of the setting reaction in a restoration and the time sufficient hardening has occurred to allow subsequent clinical procedures to be performed on the surface of the restoration. Useful modifying agents include, e.g., alkanolamines such as ethanolamine and triethanolamine, and mono-, di-, and tri-sodium hydrogenphosphates. Modifying agents can be added to either part A or part B. When used, they are present at a concentration between about 0.1 to 10 percent by weight, based on the total composition weight.
Stabilizers provide color stability. Suitable stabilizers include oxalic acid, sodium metabisulfite, sodium bisulfite, sodium thoisulfate, metaphosphoric acid, and combinations thereof.
Free radical stabilizers can be used with the photoinitiator to prevent premature polymerization or to adjust the working time in free radical systems. Suitable examples of free radical stabilizers include, e.g., butylated hydroxytoluene (BHT) and methyl ethyl hydroquinone (MEHQ).
Submicron silica particles improve the handling properties. Suitable silica particles include pyrogenic silicas such as AEROSIL series OX 50, 130, 150, 200, and R-812S, available from Degussa Corp., and CAB-O-SIL M5 silica available from Cabot Corporation.
In one embodiment, the invention is conveniently provided in the form of a kit. In the kit, part A and part B can be provided in a variety of containers, such as tubes, syringes, bottles, dual barrel syringes, auto-mix systems, titurable capsules, and foil packages. An illustrative kit contains a dual barrel syringe having a first barrel and a second barrel. Part A resides in the first barrel and Part B resides in the second barrel. Part A is a dispersion that comprises, e.g., at least one polyacid, at least one polymerizable component, and an oxidizing agent, where the polyacid and/or the oxidizing agent is dispersed in the polymerizable component. Part B comprises water, reactive fillers, and at least one reducing agent where the reducing agent can be dispersed in polymerizable component. In use, a portion of parts A and B, would be dispensed onto a mixing pad. The user would mix the two parts together, typically by hand, and apply the composition to a patient""s dental structure. The kit may optionally contain items, including but not limited to, instructions, adhesive systems, restorative material, instruments, mix pads, prosthesis, or other materials used in a dental procedure.